tbuckley/cabot-search huggingface dataset:
Fear of cancer recurrence inventory scores and their correlation with quality of life and stress levels in breast cancer survivors.
Authors: Christy Morrissey, Kristin Szuhany, Matteo Malgaroli, Emma Jennings, Marleen Iva Meyers, Stephen Ross, Sylvia Adams, Naomi Simon
Journal: Journal of Clinical Oncology (2023)

e24073 Background: For survivors of early stage breast cancer, the fear of cancer recurrence (FCR) can be distressing. A clinical challenge is recognizing which patients reporting FCR may need psychological intervention. Prior studies have suggested clinically significant FCR if the validated FCR Inventory (FCRI) scale score is &gt; = 22 while others suggest as low as &gt; = 13 may be an optimal threshold. Our goal was to understand the optimal thresholds for detection of clinically significant impairments in quality of life and high levels of stress. We thus examined FCRI thresholds that optimized detection with two standardized screening modalities of quality of life and perceived stress respectively: the Functional Assessment of Cancer Therapy-General (FACT-G) and the Perceived Stress Scale (PSS). Methods: A previously published cohort of breast cancer survivors at our institution consented to complete self-reported psychological measures and gave access to their medical records. The 2 measures being compared to the FCRI were PSS and FACT-G. FCRI, is a 9-item self-report measure, that evaluates worry about health status and illness returning, triggers that influence worry, uncertainty, and the concerns of significant others. FACT-G, a 28-item self-report measure, assesses quality of life in cancer patients, including physical well-being, social/family well-being, emotional well-being, and functional well-being; we examined the binary threshold score for reduced health related quality of life ( &lt; = 62) vs not reduced health related quality of life (&gt; 62). PSS, assesses the degree to which situations in one’s life are appraised as stressful; we examined the threshold score for low stress (0-13) vs moderate or high stress ( &gt; 13). Sensitivity (Sen) and specificity (Spe) were calculated for each cutoff value for the FCRI score between 16 and 22 (two proposed cutoffs) when compared to the FACT-G and the PSS binary cut points. Results: A total of 177 breast cancer survivors participated in the study. The mean age of participants was 57.6 (SD 13.1) years. Mean scores were 18.6 (SD 7.5) for the FCRI (n = 170), 13.92 (SD 7.0) for the PSS (n = 176) and 80.6 (SD 14.9) for the FACT-G (n = 155). FCRI &gt; = 20 appeared to optimize sensitivity and specificity both on the FACT-G (Sen: 82.4, Spe: 56.1) and PSS (Sen: 63.2 Spe: 69.1) in our patient population. Conclusions: Our results suggest that a FCRI cutoff of 20 may optimize inclusion of patients likely to have poorer quality of life and higher levels of stress. This may allow for more patients in this vulnerable population to be identified for possible intervention, without losing specificity to those with significant distress.[Table: see text]
Longitudinal assessment of cardiac involvement in Erdheim-Chester disease using cardiac magnetic resonance imaging.
Authors: Levi-Dan Azoulay, Marine Bravetti, Fleur Cohen-Aubart, Zahir Amoura, Jean-Philippe Spano, Philippe Cluzel, Julien Haroche
Journal: Journal of Clinical Oncology (2023)

7067 Background: Erdheim-Chester disease (ECD) is a rare multi-systemic non-Langerhans cell histiocytosis that affects the heart in nearly half of patients. Atrial infiltration and pericardial effusion are the hallmarks of cardiac involvement and can lead to clinical complications (conduction disorders, coronary artery stenosis, tamponade, constrictive pericarditis). Evolution under treatment is poorly studied. We aimed to investigate the evolution of cardiac involvement in ECD using cardiac magnetic resonance (CMR) imaging. Methods: All ECD patients with a CMR imaging disclosing a cardiac involvement and who underwent at least one follow-up CMR imaging between 2005 and 2020 at a French tertiary center were retrospectively included. First and last CMR imaging were compared. Multivariable analysis was performed to search for independent predictors of cardiac involvement resolution. Variables were included in the model if their P-value was &lt; 0.1 on univariable analysis. Results: Overall, 46 patients were included. Median age at first imaging was 63 years [53-69]. Median delay between the first and the last imaging was 4 years [2-7]. BRAF V600E mutation was present in 43 patients (94%). Patients received a median of 2 [1-3] treatments. All patients (100%) had cardiac involvement at baseline. Right atrio-ventricular sulcus (RAVS) was infiltrated in 38 patients (83%) and was the main cardiac feature.Overall, complete regression was observed in 6 patients (13%), partial regression in 26 patients (56%), stable imaging in 12 patients (26%), and worsening in 2 patients (5%). In patients with RAVS infiltration, complete regression was observed in 5 patients (16%) and partial regression was seen 22 patients (58%) regression. On univariable analysis, patients with regression of their infiltration had a lower rate of death (16% versus 64%, P= 0.002), a higher rate of atrial infiltration late gadolinium enhancement (LGE) (97% versus 71%, P= 0.01), a higher rate of hydronephrosis (50% versus 14%, P= 0.03) and a lower rate of interferon prescription (69% versus 100%, P= 0.02). A similar rate of vemurafenib use was observed in both groups (69% versus 54%, P= 0.3). On multivariable analysis, death remained significantly associated with follow-up imaging status (ß = -2.3 P= 0.01), while atrial infiltration LGE (ß = 2.7, P= 0.06), hydronephrosis (ß = 1.6, P= 0.1) and treatment with interferon (ß = -16, P= 1) were no longer significantly associated with imaging status. Conclusions: Partial or complete resolution of cardiac involvement was observed in 69% of patients with ECD and was significantly associated with a lower rate of death on multivariable analysis.
Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis.
Authors: Lianna Jean Marks, Victor Ritter, Liora M. Schultz, Eric J. Lowe, Catherine Aftandilian
Journal: Journal of Clinical Oncology (2023)

10032 Background: Treatment options for relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK)-inhibitors. However, there is no standard treatment and limited published data evaluating their use in this patient population. Methods: We conducted a retrospective, multi-institutional study of patients &lt;22 yrs old at initial diagnosis with R/R ALCL treated between 2011-2021 across 18 institutions. Results: We identified 85 patients with R/R ALCL (median age at initial diagnosis 12 yrs, 67% male, 96% ALK+). Treatment for initial diagnosis included ALCL99 (31%), ANHL12P1 + BV (32%), ANHL12P1 + crizotinib (CZ) (11%), ANHL0131 (14%), or other (13%). Median time from diagnosis to relapse was 0.7 yrs (range 0.2-10.8 yrs) with sixteen patients (18%) relapsing on initial chemotherapy. Stage at relapse for 82 ALK+ patients: I (9%), II (15%), III (41%), IV (35%). Initial re-induction regimens shown in the table. Fifty-nine (72%) patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 49 allogeneic with one receiving both. Of 59 transplanted patients, 10 relapsed (6 allo 4 auto) and 7 died. All but one of the patients who relapsed post-HSCT responded to additional therapy and remain alive. Of 23 ALK+ patients who never had a transplant, 4 patients died and 19 are alive in remission. Eleven remain on active therapy (6 CZ, 3 BV, 1 BV+CZ, 1 vinblastine) with eight off therapy. Patients who received a transplant more likely to be off therapy and alive. Duration of treatment for patients receiving BV or the ALK-inhibitor CZ varied widely (BV 1-11 yrs; CZ 2-10 yrs) with 20 patients continuing on therapy at the time of data collection. Five-year overall survival for patients with or without transplant was 91% (CI 84-99%) and 86% (CI 73-100%) respectively. Conclusions: This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy. Transplant may not be necessary for all R/R patients including those with high-risk disease. [Table: see text]
African American women who carry the <i>BRCA1/2</i> mutation: Clinical characteristics and prevention strategies.
Authors: Ujjwal Karki, Bipin Ghimire, Shiva Shrotriya, Tara Rangarajan, Dana Zakalik
Journal: Journal of Clinical Oncology (2023)

10554 Background: Carriers of pathogenic variants (PV) in BRCA1/2 have an increased risk of breast, ovarian, and other cancers . The clinical characteristics and uptake of risk-reducing interventions in African American(AA) women with BRCA1/2 PVs are less well studied. Methods: After IRB approval, we performed a retrospective chart review on African American women seen at Nancy and James Grosfeld Cancer Genetics Center at Beaumont Health from January 1, 2006, to December 31, 2021, who tested positive for a BRCA 1/2 mutation. We analyzed demographics, cancer characteristics, outcomes, and prevention strategies. Results: Of 238 African American(AA) women who underwent genetic testing, 69 patients (29%) were identified to be a carrier of BRCA1/2 PVs or likely pathogenic variants (LPVs). The median age at testing was 49 years (range: 24-87). Forty-six women (67%) had a cancer diagnosis, with a median age at diagnosis of 52 years. Four women had two, and one had three cancers, for a total of 52 cancers. Breast cancer was the most common type of cancer (40; 77%), with a median age at diagnosis of 48 years (range 24-73) and a majority (26; 65%) being BRCA2 carriers. Most were invasive ductal carcinoma (87.8%), high-grade (80%), ER-positive (52%), PR-negative (68%), HER2-negative (94%) and stage I or II disease (63%). Fifteen (38%) were triple-negative. Most patients (87%) received adjuvant systemic chemotherapy or endocrine therapy, 31% received neoadjuvant chemotherapy, and 39% received adjuvant radiation. The 3- and 5-year survival was 94% and 91%, respectively, with a median follow-up of 103 months. Three patients (all BRCA2 carriers ) developed contralateral breast cancer (median time to recurrence: 201 months); 3 (all BRCA2) developed local recurrence (median time to recurrence: 60 months), and 4(2 BRCA1, 2 BRCA2) developed metastatic recurrence (median time to recurrence: 34 months). Other cancers observed were ovarian (n = 6; 4 BRCA2, 2 BRCA1), uterine (2), lung (2), kidney (1), and glioblastoma (1). Compared to AA carriers without cancer, those with cancer were more likely to undergo risk-reducing mastectomy (RRM; 68% vs. 23%) and risk-reducing salpingo-oophorectomy (RRSO; 72% vs. 55%). In the non-cancer group, significantly fewer patients elected RRM (23%) compared to RRSO (55%). Conclusions: Our study outlines the characteristics of AA women who carry BRCA1/2 PVs, revealing that most had high-grade invasive ductal breast cancer with excellent survival. Patients without a cancer diagnosis were less likely to undergo risk-reducing surgery, highlighting the importance of effective counseling focusing on primary prevention in these high-risk patients. Further research is needed to better characterize cancer risk and address potential barriers to uptake of risk-reducing interventions in this population.
Characterizing imposter syndrome among oncologists on social media.
Authors: Eleonora Teplinsky, Sara Beltran Ponce, Don S. Dizon, Narjust Florez, Matthew S. Katz, Lindsey Allison McAlarnen, Scott Moerdler, Martina Cathryn Murphy, Hina Saeed, Maura Meredith Barry
Journal: Journal of Clinical Oncology (2023)

11018 Background: Imposter syndrome (IS) is defined as an inability to believe that one’s success is deserved. It is commonly encountered by physicians, with cited statistics ranging from 22% to 98%, is associated with negative mental health impacts and can be harmful to one’s wellbeing. Given increasing SM use in hematology/oncology (H/O), we aimed to evaluate the effect of SM on IS among oncology trainees and oncologists. Methods: An anonymous online survey was distributed to oncology trainees and oncologists through SM platforms (Twitter, Facebook (FB), Instagram (IG)) and e-mail. Questions included demographics, current SM use, a novel scale for IS on SM (Table), Young Imposter Syndrome (YIS) Scale (a validated IS instrument) &amp; assessment of mental health impacts of SM. Results: Out of 195 respondents, 103 answered all questions; median age 40y (27-65), 81% female. 21% were trainees and 36%, 30%, and 12% were early, mid and late-career faculty, respectively. Specialties included: adult H/O (72%), gynecologic oncology (11.3%), radiation oncology (10.5%), surgical oncology (4.1%), and pediatric H/O (1.5%). Twitter was the most commonly used SM platform (68%) followed by FB (36%) &amp; IG (20%). 26% utilized professional SM 0-1 times/week while 28% did so daily. 97/157 (62%) noted positive mental health impacts from SM. 41% felt anxious, lonely or depressed due to SM. 19.7% have experienced SM harassment or cyberbullying. More than 50% of respondents met criteria on the YIS and IS scale; indeed, the YIS and IS on SM Scales were significantly correlated with each other (r = 0.57, p &lt; 0.001, N = 103). The presence of IS on SM was associated with gender but not race/ethnicity or career stage. 59% of females versus 28% of males met criteria for IS (p = 0.02). The presence of IS on SM was significantly associated with self-perceived IS in professional settings (p &lt; 0.001), but not in personal settings (p = 0.21). Conclusions: Many oncology professionals experienced IS while interacting on SM, but also note a positive mental health impact with SM use. The presence of IS on SM correlated with results on the YIS Scale, suggesting a novel assessment method, but further validation is needed. Future efforts to combat IS on SM while enhancing positive aspects of medical SM are warranted. [Table: see text]
Identification of a novel <i>NPM1</i> mutation in acute myeloid leukemia.
Authors: Yiyi Yao, Xiangjie Lin, Chen Wang, Ying Gu, Hong-Hu Zhu, Jie Jin, Yinghui Zhu, Huafeng Wang
Journal: Journal of Clinical Oncology (2023)

e19019 Background: Nucleophosmin (NPM1) is predominant nucleolar localization. NPM1-mutant acute myeloid leukemia (AML) account for 25-35% of adult AML patients, has been defined as a distinct AML entity in the 2022 WHO classification. The majority of NPM1 mutations reported affect exon 12 (classical type A mutation), account for 75-80% of adult NPM1-mutated AML cases, which generate an extra nuclear export signal (NES) in the C-terminal leading to aberrant cytoplasmic localization. Similar aberrant cytoplasmic translocation has also been reported in NPM1 mutants that identified in exons 9 and 11. Identification of novel non-type A mutants is paramount for diagnosis, risk stratification, and prognosis for targeted population. Methods: Somatic mutation analysis is performed on 566 AML patients using next-generation sequencing (NGS). Immunofluorescence and immunohistochemistry were used to identify the cytological localization of mutant NPM1. HEK-293T cells transiently transfected with plasmids for ectopic expression of the GFP-mutated NPM1 fusion proteins were treated with the specific Crm1/XPO1 inhibitor leptomycin B and to evaluate the NES dependence of their subcellular localization. Results: We identified one AML patient with NPM1 mutant located on exon 5. This patient was a 59-year-old female with de novo AML, with an 18-nucletide in-frame insertion at position 405 (c.405_406insGCCCTGGAACTGGGGAAC, named MutSong) in the middle of exon 5 [variant allele fraction (VAF), 11.9%]. It generated a new NPM1 mutant protein (p.135insALELGN), and containing a leucine-rich NES. Notably, different with all NPM1 mutant in other exons reported so far, our exon 5 mutant retained the functional c-terminal but insert one leucine-rich NES, similar finding was recently reported in NPM1 mutants that identified in exon 5 but on different position. This NPM1 mutant in exon 5 resulted in cytoplasmic localization both by confocal and immunohistochemistry in AML patient sample. HEK-293T overexpressing the new GFP-NPM1 exon 5 fusion protein indicated the aberrant localization in the cytoplasm and partially in nucleoli. Moreover, NES-dependent cytoplasmic localization was inhibited by exportin-1 inhibitor leptomycin B, indicated that the novel NES generated by exon 5 mutant is responsible for cytoplasmic localization. This patient carried WT1, IKZF1, JAK2, and NUP98 mutations, and was intravenously treated with daunorubicin plus cytarabine for induction followed by 3 cycles of intermediate-dose cytarabine as consolidation. Then the patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, the patient died of severe pulmonary infection and viral encephalitis 14 months after the initial remission, 7 months after allo-HSCT. Conclusions: Our finding of the novel NPM1 mutation in exon 5 supported that beside exon 12, exon 5 mutant is another NPM1 “born to be exported” mutant critical for leukemogenesis.
Encorafenib (enco) + binimetinib (bini) + pembrolizumab (pembro) for unresectable locally advanced or metastatic BRAF V600-mutant melanoma: Results from STARBOARD safety lead-in (SLI).
Authors: Dirk Schadendorf, Reinhard Dummer, Caroline Robert, Antoni Ribas, Ryan J. Sullivan, Timothy J. Panella, Meredith McKean, Edgardo S. Santos, Jill S. Clancy, Mahgull Nazar Thakur, Anna Polli, Alessandra Di Pietro, Paolo Antonio Ascierto
Journal: Journal of Clinical Oncology (2023)

9531 Background: BRAF inhibitors (BRAFi) + MEK inhibitors (MEKi) (eg, enco + bini) and immune checkpoint inhibitors (CPIs) (eg, pembro) are approved for patients (pts) with BRAF V600-mutant metastatic melanoma. Combinations of BRAFi + MEKi with CPIs further improve outcomes and may offer additional treatment strategies. STARBOARD (NCT04657991) is an ongoing randomized, double-blinded, placebo-controlled, phase 3 study of enco + bini + pembro vs pembro in pts with unresectable locally advanced or metastatic BRAF V600-mutant cutaneous melanoma. Here we present the SLI results. Methods: Key inclusion criteria were histologically confirmed unresectable/metastatic BRAF V600E/K-mutant cutaneous melanoma and ≤1 prior systemic therapy for unresectable/metastatic disease. Pts received enco 450 mg QD + bini 45 mg BID + pembro 200 mg IV Q3W (COMBO450+P) or enco 300 mg QD + bini 45 mg BID + pembro 200 mg IV Q3W (COMBO300+P). The primary objective was to identify the recommended phase 3 dose (RP3D). The primary endpoint was dose-limiting toxicity (DLT) incidence; secondary endpoints included safety, objective response rate (ORR), time to response (TTR), and PFS (post hoc). Results: 20 pts received COMBO450+P and 17 COMBO300+P (cutoff: Dec 2, 2022). See table for baseline characteristics. 1 pt had a DLT with COMBO450+P: Grade (G) 3 drug-induced liver injury with concurrent G4 ALT increase and G3 bilirubin increase that resolved. 2 pts had DLTs with COMBO300+P: 1 with G3 rheumatoid arthritis flare and 1 with inability to receive drug due to G4 arthralgia, G4 back pain, G4 pyrexia, G3 chills, G3 headache, G3 paranesthesia, and G3 maculopapular rash. Drug-related AEs led to permanent discontinuation in 4, 5, and 6 pts for enco, bini, and pembro, respectively. 1 pt in the COMBO300+P arm died &lt;28 days after discontinuing all study treatments due to disease progression. See table for antitumor activity data. Conclusions: Safety across cohorts was comparable and consistent with the known safety profile of each agent. Both regimens were generally tolerable; COMBO450+P was chosen as the RP3D based on the totality of the safety data. The phase 3 portion of STARBOARD is ongoing. Clinical trial information: NCT04657991 . [Table: see text]
Adherence to surveillance guidelines in survivors of hodgkin lymphoma: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Jamie Michelle Shoag, Yan Chen, Yutaka Yasui, Kirsten K. Ness, Wendy M. Leisenring, Joseph Philip Neglia, Melissa M. Hudson, Kevin C. Oeffinger, Gregory T. Armstrong, Tara O. Henderson, Paul C. Nathan
Journal: Journal of Clinical Oncology (2023)

10047 Background: Pediatric Hodgkin lymphoma (HL) is a highly curable disease. However, survivors are at high risk for long-term complications of therapy. The impact of sociodemographic and clinical factors on adherence to late effects surveillance guidelines is unknown. Methods: The CCSS is a retrospective cohort with prospective follow-up of survivors diagnosed from 1970-1999. HL survivors enrolled in CCSS who responded to a 2017 questionnaire were included. We assessed adherence to the Children’s Oncology Group surveillance guidelines for cardiomyopathy, breast cancer, colorectal cancer, and skin cancer. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (aOR [95% CI]) for sociodemographic and clinical risk factors associated with adherence. Estimates were adjusted for area deprivation index (ADI); chronic health conditions; recent (≤2 years) routine check-up, cancer center or survivorship clinic visit; and possession of a survivorship care plan (SCP). Results: 1,380 HL survivors (45.6% male; median age 43.6 years, range 21.6-65.9 years) responded, of whom 55.5% were at elevated risk for cardiac dysfunction, 71.0% for breast cancer, 83.5% for skin cancer, and 39.4% for colorectal cancer. Of those at elevated risk, 42.7%, 19.9%, 31.3% and 48.9% were adherent to the guidelines for cardiac, breast, skin, and colorectal screening, respectively. Predictors of adherence to cardiac dysfunction guidelines were male sex (aOR 1.7 [1.1-2.6]), having children (aOR 1.6 [1.1-2.4]), recent routine checkup (aOR 4.0 [1.3-13.1]), recent visit to a cancer center or survivorship clinic (aOR 6.2 [3.9-10.0]), and possession of a SCP (aOR 3.1 [1.9-5.0]). Adherence to breast cancer guidelines was higher in those who were unmarried (aOR 2.1 [1.0-4.1]), had a recent visit to a cancer center or survivorship clinic (aOR 3.7 [2.0-7.0]), and possessed a SCP (aOR 3.5 [1.5-8.3]). Adherence to skin cancer guidelines was higher in those &gt; 14 years at diagnosis (aOR 1.8 [1.3-2.4]), living in a low deprivation area (ADI 1-24.9) compared to a high deprivation area (ADI 75-100) (aOR 3.4 [1.9-5.9]), employed (aOR 1.8 [1.1-2.9]), &gt; 30 years from diagnosis (aOR 2.4 [1.6-3.6]), with a recent routine check-up (aOR 3.6 [1.1-12.5]), and recent cancer care (aOR 2.4 [1.6-3.5]). Adherence to colorectal cancer guidelines was higher in those with grade 3-4 chronic health conditions (aOR 1.9 [1.1-3.3]). Conclusions: Less than 50% of HL survivors are adherent to screening guidelines. Sociodemographic risk factors are significant predictors of non-adherence, particularly to skin cancer screening guidelines. This threatens to potentiate outcome disparities among HL survivors.